Morphogenesis of epithelial tissues such as the skin involves complex interplay of autonomously generated forces, cell-cell interactions, and the extracellular matrix. The C. elegans epidermis is a model epithelium whose development can be dissected with single cell resolution. Our studies address three aspects of epidermal development. First, in embryonic epidermal enclosure the epidermal epithelium spreads over substrate neurons. Using semi- automated cell tracking we that the neuronal substrate is highly dynamic during enclosure. We will address how these collective neuronal migrations are driven and their relationship to epidermal spreading movements. Our second aim addresses the function of a family of secreted enzymes, the peroxidasins, in epidermal development and wound healing. Epithelial spreading movements and wound healing processes may share related mechanisms. We have developed a model for epidermal wound healing in C. elegans. We will characterize the role of calcium signaling in wound repair in the epidermis. We will use genetics to analyze a mutant that appears to undergo spontaneous epidermal wounding. These three aims will explore interrelated aspects of epidermal morphogenesis and repair. A better understanding of these processes will shed light on functions of conserved signaling pathways in development and will improve our knowledge of the molecular basis of wound repair. PUBLIC HEALTH RELEVANCE: The proposed work is aimed at understanding the genetic basis of tissue morphogenesis, focusing on how cells interact during the development of the skin and nervous system. Increased understanding of this process has implications for human birth defects such as neural tube closure. Understanding similarities between epithelial morphogenesis and wound healing will elucidate how epidermal cells sense and respond to damage.